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ARTICLE IN BRIEF

In a comparison of anterior temporal lobectomy and stereotactic radiosurgery for mesial temporal lobe epilepsy, a higher proportion of patients receiving standard surgery were seizure free, and the difference in patients experiencing verbal memory loss was not significantly different between the two procedures.

Standard anterior temporal lobectomy appears to be superior to stereotactic radiosurgery for mesial temporal lobe epilepsy, according to a report on the Radiosurgery or Open Surgery for Epilepsy (ROSE) trial in the March 30 online edition of Epilepsia.

A higher proportion of patients receiving standard surgery were free of seizures, and the difference in patients experiencing verbal memory loss was not significantly different between the procedures, according to the report.

“Compared to historical controls from similar patients randomized to optimal medication treatment, both radiosurgery and conventional surgery are effective with conventional surgery being a bit more effective,” said study co-author, Paul A. Garcia, MD, professor of neurology at the University of California, San Francisco. “Conventional surgery usually works right away while radiosurgery takes many months to stop the seizures. In light of this, most patients with temporal lobe epilepsy and mesial temporal sclerosis should have conventional surgery rather than radiosurgery.”

Prospective, multicenter studies of gamma knife surgery for mesial temporal lobe surgery, in use since 1995, have shown seizure remission rates comparable to anterior temporal lobectomy, and a multicenter trial in the United States of stereotactic radiosurgery showed that verbal memory loss was spared compared to standard surgery. However, the current study reported in Epilepsia is the first randomized control trial comparing the two procedures.

STUDY DESIGN

In the study, a total of 58 patients were randomized to stereotactic radiosurgery (n=31) or anterior temporal lobectomy (n=27). The stereotactic radiosurgery protocol consisted of a single outpatient session of a 24-Gy dose delivered at a volume between 5.5 and 7.5 cm2 comprising the amygdala, anterior 2 cm of hippocampus, and parahippocampal gyrus. Anterior temporal lobectomy consisted of resection of 1-2 cm of the anterior superior temporal gyrus and 3 cm of the anterior middle and inferior temporal gyri, the temporal portion of the amygdala, the anterior 2-3 cm of the hippocampus, and adjacent entorhinal cortex.

Patients were evaluated in person every three months for the first 18 months and then at 24, 30, and 36 months supplemented with telephone interviews every three months for the last 18 months. Neurologists blinded to the surgery method reviewed seizure diaries at each treatment center. The research team defined seizure freedom as the absence of seizures that caused impairment of consciousness between months 25 and 36.

Dr. Garcia said that while anterior temporal lobectomy was clearly shown to be superior, the results for stereotactic radiosurgery reveal the procedure to be reasonably effective, which may make it preferable for some patients. “For patients with medical conditions that make conventional surgery too risky — such as hematologic conditions promoting bleeding — or preferences to avoid conventional surgery, radiosurgery can be an effective alternative,” he said.

He said an important strength of the study is that it was randomized and assessed by blinded clinicians, which avoided biases seen in earlier reports.

“The principal weakness is that the number of people recruited only allows us to be confident about large differences in outcomes,” Dr. Garcia said.

EXPERT COMMENTARY

Experts who reviewed the report for Neurology Today agreed the study was well designed and its results are conclusive and convincing. “The results leave little doubt that stereotactic radiosurgery is inferior to anterior temporal lobectomy for treatment of intractable epilepsy due to mesial temporal sclerosis,” said Michael R. Sperling, MD, FAAN, editor of Epilepsia and director of Jefferson Comprehensive Epilepsy Center at the Sidney Kimmel Medical College of Thomas Jefferson University.

“The difference in seizure outcome is striking, even with the relatively small number of cases, and stereotactic radiosurgery was associated with a significant rate of adverse effects,” Dr. Sperling said. “Not only do fewer patients achieve seizure freedom, but surgical response is immediate, whereas stereotactic radiosurgery requires two years for full effect. The study has no significant weaknesses, though the lower than expected recruitment limits the confidence intervals for efficacy of both procedures.”

“The ROSE trial confirms my clinical impression — the delay in response to stereotactic radiosurgery is unacceptably long, and given the associated risks of uncontrolled epilepsy, it is a suboptimal method of treatment,” Dr. Sperling said. “This would be true even if long-term response rates were similar, for I would not want to wait one and a half to two years for therapy to become effective if I had an alternative that promptly produced seizure remission. During that time, patients may die, suffer injury, and remain disabled. The lack of significant difference in memory outcome is also striking; the less invasive procedure, stereotactic radiosurgery, produces a similar level of verbal memory deficit as open surgery.”

Jerome Engel Jr., MD, PhD, FAAN, director of the University of California, Los Angeles (UCLA Seizure Disorder Center at the David Geffen School of Medicine at UCLA, agreed. “The results are not surprising,” he said. “The stereotactic radiosurgery effect on seizures is not immediate and can take months or a year or more to occur. During that time the patient continues to have seizures.”

He added: “There was a possibility that stereotactic radiosurgery would get better results with respect to verbal memory loss, but that doesn't appear to be the case. The only real benefit of stereotactic radiosurgery is for patients who are averse to standard surgery.”

Dr. Sperling noted that the surgical arm did not incorporate mesial temporal laser interstitial thermal ablation, which has become widely used in the past few years and often substitutes for anterior temporal lobectomy when treating mesial temporal sclerosis. “Whether stereotactic radiosurgery's long-term efficacy differs from that would be worth knowing,” he said. He added that a single-arm trial assessing efficacy of thermal ablation currently underway may at least partially answer that question.

“Mesial temporal thermal ablation is a good alternative in my view,” he told Neurology Today. “We are still learning about its efficacy, but the risk and tolerability are considerably lower than anterior temporal lobectomy in my experience, so it is a good option for many patients. Patients treated with laser technology typically spend only one day in the hospital and can return to work and full activity in two to three days. They have minimal discomfort and avoid the risks and pain of an open craniotomy, as is needed for anterior temporal lobectomy. I hope the efficacy will prove to be similar to that of anterior temporal lobectomy, but even should efficacy prove to be somewhat less, the strikingly reduced morbidity would still lead me to advise it as a treatment. Patients can always undergo an anterior temporal lobectomy should it fail, and every patient who avoids that procedure gains.”

Dr. Engel said he believes the superiority of laser ablation is yet to be proven. And he questioned whether patients who fail to respond to ablation would be willing to undergo yet another surgery. “Supporters say you can always go back and do standard surgery, but that's a lot of procedures and patients may just say, ‘that's enough.’”